Receptor for advanced glycation end products on human synovial fibroblasts: Role in the pathogenesis of dialysis-related amyloidosis
Receptor for advanced glycation end products on human synovial fibroblasts: Role in the pathogenesis of dialysis-related amyloidosis
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DOI：
10.1681/asn.v1351296
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发表时间：
2002-05-01
影响因子：
13.6
通讯作者：
Owen, WF
中科院分区：
文献类型：
--
作者：
Hou, FF;Jiang, JP;Owen, WF
透析相关性淀粉样变性（AML）中淀粉样纤维的一种重要成分是经晚期糖基化终产物（AGE）修饰的β 2-微球蛋白（β 2 m）。淀粉样沉积物主要位于关节结构中。伴有以单核细胞浸润为特征的邻近慢性炎症反应。本研究检测了AGE-beta（2）m与人滑膜成纤维细胞的相互作用，并研究了这种相互作用的促炎作用。结果表明，人滑膜成纤维细胞组成型表达AGE（AGE）受体。在滑膜内膜中主要检测到hepatocellular的表达，在滑膜内膜中表达上调。I-125-AGE-β（2）m以特异性、剂量依赖性方式与固定化的人滑膜成纤维细胞结合（Kd约为138.0 nM），且结合被抗AGEs IgG抑制。用AGE-β（2）m孵育人滑膜成纤维细胞可诱导这种AGE修饰蛋白的降解，以及单核细胞趋化蛋白-1（MCP- 1）mRNA和蛋白表达的增加。由AGE-β（2）m刺激的人滑膜成纤维细胞产生的MCP-1的量足以诱导单核细胞的趋化性。MCP-1的合成是由于MCP-1的参与，因为MCP-1合成的增加被人滑膜成纤维细胞与抗MCP-1 IgG的预孵育所减弱。这些数据提供了RAGE介导的人滑膜细胞扰动的证据。其可能参与与炎症相关的炎症过程的发病机制。
An important component of amyloid fibrils in dialysis-related amyloidosis (DRA) is beta(2)-microglobulin (beta(2)m) modified with advanced glycation end products (AGE). The amyloid deposits are located principally in joint structures. with adjacent chronic inflammatory reaction characterized by monocyte infiltration. This study examined the interaction of AGE-beta(2)m with human synovial fibroblasts and investigated the proinflammatory effects of that interaction. It was demonstrated that human synovial fibroblasts constitutively expressed the receptor for AGE (RAGE). RAGE expression was detected mainly in synovial intima and was upregulated in DRA synovium. I-125-AGE-beta(2)m bound to immobilized human synovial fibroblasts in a specific, dose-dependent manner (K-d of approximately 138.0 nM), and binding was inhibited by anti-RAGE IgG. Incubation of human synovial fibroblasts with AGE-beta(2)m induced degradation of this AGE-modified protein, as well as increased monocyte chemoattractant protein-1 (MCP- 1) mRNA and protein expression, The amount of MCP-1 produced by AGE-beta(2)m-stimulated human synovial fibroblasts was sufficient to induce the chemotaxis of monocytes. MCP-1 synthesis resulted from engagement of RAGE, because the increase in MCP-1 synthesis was attenuated by preincubation of human synovial fibroblasts with anti-RAGE IgG. These data provide evidence of RAGE-mediated perturbation of human synoviocytes. which may be involved in the pathogenesis of inflammatory processes associated with DRA.